title: Methylation-mediated gene silencing of suppressor of cytokine signaling-1 (SOCS-1) gene in esophageal squamous cell carcinoma patients of Kashmir valley.
abstract: BACKGROUND
  Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths in Jammu and Kashmir. The negative regulation of tumor suppressor gene leading to change in signaling pathway is one of the major mechanisms responsible for tumorigenic transformation.
  
  
  OBJECTIVE
  In the present study, the role of silencing of suppressor of cytokine signaling-1 (SOCS-1) gene, a negative regulator of JAK/STAT pathway, was analyzed in ESCC.
  
  
  METHODS
  The expression pattern of SOCS-1 gene was analyzed in esophageal tumor biopsies although normal adjacent tissues that served as controls. Reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry, methylation-specific PCR (MSP), and human papillomavirus (HPV) detection were performed to assess the expression pattern and promoter methylation of SOCS-1 gene including HPV status in a total of 75 surgically resected tissue specimens.
  
  
  RESULTS
  Compared with the level of SOCS-1 expression in normal tissues, 53% (40/75) of the tumor tissues expressed either undetectable or reduced SOCS-1 expression (>50% loss of expression), which was significantly associated with advanced clinical stage or severe histopathological grade of the disease (P < 0.01). Aberrant promoter methylation of the SOCS-1 gene was found in 45% (34/75) of the esophageal tumor tissues, which was also found to be significantly associated with advanced stage of esophageal carcinoma (P < 0.01). The prevalence of HPV infection was found in 19% of tumor cases, whereas no HPV could be detected in any of the normal adjacent tissues.
  
  
  CONCLUSIONS
  Transcriptional inactivation of SOCS-1 gene, primarily due to its promoter hypermethylation although HPV infection, may play an important role in esophageal carcinogenesis in Kashmir.
authors.affiliation: Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), Noida, India.
authors.forename: Showket
authors.initials: S
authors.lastname: Hussain
authors.forename: Neha
authors.initials: N
authors.lastname: Singh
authors.forename: Irfana
authors.initials: I
authors.lastname: Salam
authors.forename: Kapil
authors.initials: K
authors.lastname: Bandil
authors.forename: M
authors.initials: M
authors.lastname: Yuvaraj
authors.forename: Mohammad
authors.initials: M
authors.lastname: Akbar Bhat
authors.forename: Mohammad
authors.initials: M
authors.lastname: Muzaffar Mir
authors.forename: Mushtaq A
authors.initials: MA
authors.lastname: Siddiqi
authors.forename: Ranbir C
authors.initials: RC
authors.lastname: Sobti
authors.forename: Mausumi
authors.initials: M
authors.lastname: Bharadwaj
authors.forename: Bhudev C
authors.initials: BC
authors.lastname: Das
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000821:virology; D019175:DNA Methylation / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000821:virology; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D007194:India; D027383:Papillomaviridae / Q000502:physiology; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins